ONCOLOGY LETTERS 6: 1465-1469, 2013
Inhibition of the mammalian target of rapamycin leads to autophagy activation and cell death of MG63 osteosarcoma cells ZONG‑GANG XIE*, YE XIE* and QI‑RONG DONG Department of Orthopedic Surgery, The Second Affiliated Hospital, Soochow University, Suzhou, Jiangsu 215006, P.R. China Received January 7, 2013; Accepted June 27, 2013 DOI: 10.3892/ol.2013.1531 Abstract. It has been well documented that the inhibition of the mammalian target of rapamycin (mTOR) induces autophagy in proliferative cells. Therefore, mTOR inhibitors have been proposed for the treatment of cancer. As autophagy plays significant roles in tumor cell survival, the present study aimed to investigate the contribution of autophagy activation to the antitumor effects of cis‑diamminedichloroplatinum (CDDP). An MTT assay was used to determine the cytotoxic effects of rapamycin on MG63 osteosarcoma cells. The cell cycle was assessed using a flow cytometry analysis subsequent to staining the DNA with propidium iodide. The mitochondrial membrane potential (Δψ) was measured using the fluorescent probe, JC‑1. Western blot analysis was used to determine the expression of the proteins that are involved in apoptosis and autophagy, including p53, p62, light chain 3 (LC3) and Beclin‑1. The viability of the MG63 cells was inhibited following rapamycin or CDDP treatment. The mitochondrial Δψ collapsed following treatment with rapamycin or CDDP. Rapamycin induced cell death and enhanced the effects of the induction of MG63 cell death by CDDP. Western blot analysis detected the induced expression of the p53 and Beclin‑1 proteins and the autophagic proteins, LC3 and p62. Rapamycin was observed to induce the death of cancer cells through apoptotic and autophagic mechanisms. Rapamycin may enhance the effects of the activation of autophagy and the induction of apoptosis by CDDP. Introduction Osteosarcoma is the most commonly diagnosed primary malignant tumor of the bone (1,2). The contemporary
Correspondence to: Professor Qi‑Rong Dong, Department of
Orthopedic Surgery, The Second Affiliated Hospital, Soochow University, 1055 San Xiang Road, Suzhou, Jiangsu 215006, P.R. China E‑mail:
[email protected] *
Contributed equally
Key words: mammalian target of rapamycin, rapamycin, autophagy, chemotherapy
treatment of osteosarcoma requires multidisciplinary therapy, incorporating surgery and systemic chemotherapy (1,3). The prognosis of osteosarcoma patients has significantly improved with the advent of chemotherapy. In the pre‑chemotherapy era, when patients underwent surgery as the only form of treatment, the survival rate was
